Research article summary (published 9 Jan 2008):

Dissecting the ER-associated degradation of a misfolded polytopic membrane protein.

Full Abstract

It remains unclear how misfolded membrane proteins are selected and destroyed during endoplasmic reticulum-associated degradation (ERAD). For example, chaperones are thought to solubilize aggregation-prone motifs, and some data suggest that these proteins are degraded at the ER. To better define how membrane proteins are destroyed, the ERAD of Ste6p(*), a 12 transmembrane protein, was reconstituted. We found that specific Hsp70/40s act before ubiquitination and facilitate Ste6p(*) association with an E3 ubiquitin ligase, suggesting an active role for chaperones. Furthermore, polyubiquitination was a prerequisite for retrotranslocation, which required the Cdc48 complex and ATP. Surprisingly, the substrate was soluble, and extraction was independent of a ubiquitin chain extension enzyme (Ufd2p). However, Ufd2p increased the degree of ubiquitination and facilitated degradation. These data indicate that polytopic membrane proteins can be extracted from the ER, and define the point of action of chaperones and the requirement for Ufd2p during membrane protein quality control.

Author information

Author/s: Nakatsukasa, Kunio (K); Huyer, Gregory (G); Michaelis, Susan (S); Brodsky, Jeffrey L (JL);

Affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.

Grants: GM51508 (Agency:NIGMS NIH HHS) ; GM75061 (Agency:NIGMS NIH HHS) ; R01 GM075061-01A1 (Agency:NIGMS NIH HHS) ; R01 GM075061-02 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Cell (Cell), published in United States. (Language: eng)

Reference: 2008-Jan; vol 132 (issue 1) : pp 101-12

Dates: Created 2008/01/14; Completed 2008/03/26; Revised 2009/09/03;

PMID: 18191224, status: MEDLINE (last retrieval date: 9/4/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

ATP-Binding Cassette Transporters - chemistry; metabolism Adenosine Triphosphatases - metabolism Adenosine Triphosphate - metabolism Cell Cycle Proteins - metabolism Endoplasmic Reticulum - genetics; metabolism; ultrastructure Glycoproteins - chemistry; metabolism Heat-Shock Proteins - metabolism Heat-Shock Response - physiology Membrane Proteins - chemistry; metabolism Molecular Chaperones - metabolism

Molecular Chaperones - metabolism Oxidative Stress - physiology Protein Conformation Protein Folding Protein Transport - physiology Saccharomyces cerevisiae - genetics; metabolism; ultrastructure Saccharomyces cerevisiae Proteins - chemistry; metabolism Ubiquitin-Conjugating Enzymes - metabolism Ubiquitin-Protein Ligases - metabolism Ubiquitination - physiology

Associated Chemicals: ATP-Binding Cassette Transporters (0) ; Cell Cycle Proteins (0) ; Glycoproteins (0) ; Heat-Shock Proteins (0) ; Membrane Proteins (0) ; Molecular Chaperones (0) ; STE6 protein, S cerevisiae (0) ; Saccharomyces cerevisiae Proteins (0) ; Adenosine Triphosphate (56-65-5) ; Adenosine Triphosphatases (EC 3.6.1.-) ; CDC48 protein (EC 3.6.1.-) ; UFD2 protein, S cerevisiae (EC 6.3.2.19) ; Ubiquitin-Conjugating Enzymes (EC 6.3.2.19) ; Ubiquitin-Protein Ligases (EC 6.3.2.19)

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